tbuckley/cabot-search huggingface dataset:
Trends in Stimulant Prescription Fills Among Commercially Insured Children and Adults — United States, 2016–2021
Authors: Melissa L. Danielson, Michele K. Bohm, Kimberly Newsome, Angelika H. Claussen, Jennifer W. Kaminski, Scott D. Grosse, Lila Siwakoti, Aziza Arifkhanova, Rebecca H. Bitsko, Lara R. Robinson
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Prescription stimulant use, primarily for the treatment of attention-deficit/hyperactivity disorder (ADHD), has increased among adults in the United States during recent decades, while remaining stable or declining among children and adolescents (1,2). MarketScan commercial claims data were analyzed to describe trends in prescription stimulant fills before and during the COVID-19 pandemic (2016-2021) by calculating annual percentages of enrollees aged 5-64 years in employer-sponsored health plans who had one or more prescription stimulant fills overall and by sex and age group. Overall, the percentage of enrollees with one or more prescription stimulant fills increased from 3.6% in 2016 to 4.1% in 2021. The percentages of females aged 15-44 years and males aged 25-44 years with prescription stimulant fills increased by more than 10% during 2020-2021. Future evaluation could determine if policy and health system reimbursement changes enacted during the pandemic contributed to the increase in stimulant prescriptions. Stimulants can offer substantial benefits for persons with ADHD, but also pose potential harms, including adverse effects, medication interactions, diversion and misuse, and overdoses. Well-established clinical guidelines exist for ADHD care, but only for children and adolescents* (3); clinical practice guidelines for adult ADHD could help adults also receive accurate diagnoses and appropriate treatment.
JYNNEOS Vaccination Coverage Among Persons at Risk for Mpox — United States, May 22, 2022–January 31, 2023
Authors: Lauren E. Owens, Dustin W. Currie, Ellen A. Kramarow, Safana Siddique, Megan Swanson, Rosalind J. Carter, Jennifer L. Kriss, Peter M. Boersma, Florence C. Lee, Ian Spicknall, Elizabeth Hurley, Maria Zlotorzynska, Adi V. Gundlapalli
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

From May 2022 through the end of January 2023, approximately 30,000 cases of monkeypox (mpox) have been reported in the United States and >86,000 cases reported internationally.* JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended for subcutaneous administration to persons at increased risk for mpox (1,2) and has been demonstrated to provide protection against infection (3-5). To increase the total number of vaccine doses available, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) on August 9, 2022, recommending administration of the vaccine intradermally (0.1 mL per dose) for persons aged ≥18 years who are recommended to receive it (6); intradermal administration can generate an equivalent immune response to that achieved through subcutaneous injection using approximately one fifth the subcutaneous dose (7). CDC analyzed JYNNEOS vaccine administration data submitted to CDC from jurisdictional immunization information systems (IIS)† to assess the impact of the EUA and to estimate vaccination coverage among the population at risk for mpox. During May 22, 2022-January 31, 2023, a total of 1,189,651 JYNNEOS doses (734,510 first doses and 452,884 second doses)§ were administered. Through the week of August 20, 2022, the predominant route of administration was subcutaneous, after which intradermal administration became predominant, in accordance with FDA guidance. As of January 31, 2023, 1-dose and 2-dose (full vaccination) coverage among persons at risk for mpox is estimated to have reached 36.7% and 22.7%, respectively. Despite a steady decline in mpox cases from a 7-day daily average of more than 400 cases on August 1, 2022, to five cases on January 31, 2023, vaccination for persons at risk for mpox continues to be recommended (1). Targeted outreach and continued access to and availability of mpox vaccines to persons at risk are important to help prevent and minimize the impact of a resurgence of mpox.
Prevalence of Delayed or Forgone Care Due to Patient-Clinician Identity Discordance Among US Cancer Survivors
Authors: Vishal R. Patel, Arjun Gupta, Anne H. Blaes, Karen M. Winkfield, Alex B. Haynes, S. M. Qasim Hussaini
Journal: JAMA Oncology (2023)

This case-control study assesses the prevalence of patient-reported delayed or forgone care due to patient-clinician identity discordance among cancer survivors and factors associated with this barrier to care.
Racial, Ethnic, and Education Differences in Age of Smoking Initiation Among Young Adults in the United States, 2002 to 2019
Authors: Alyssa F. Harlow, Rob McConnell, Adam M. Leventhal, Renee D. Goodwin, Jessica L. Barrington-Trimis
Journal: JAMA Network Open (2023)

This cross-sectional study examines differences by race and ethnicity and education in smoking prevalence and age of smoking initiation among young adults in the US between 2002 and 2019.
Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The <scp>VICTORIA</scp> echocardiographic substudy
Authors: Burkert Pieske, Elisabeth Pieske‐Kraigher, Carolyn S.P. Lam, Vojtěch Melenovský, Karen Sliwa, Yuri Lopatin, Juan Luis Arango, M. Cecilia Bahit, Christopher M. O'Connor, Mahesh J. Patel, Lothar Roessig, Daniel A. Morris, Martin Kropf, Cynthia M. Westerhout, Yinggan Zheng, Paul W. Armstrong
Journal: European Journal of Heart Failure (2023)

Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m2 ; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI -3.8 ± 15.4 vs. -7.1 ± 20.5 ml/m2 ; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.
Ventricular stiffening and chamber contracture in heart failure with higher ejection fraction
Authors: Dejana Popovic, Alessio Alogna, Massar Omar, Hidemi Sorimachi, Kazunori Omote, Yogesh N.V. Reddy, Margaret M. Redfield, Daniel Burkhoff, Barry A. Borlaug
Journal: European Journal of Heart Failure (2023)
Predicting liver-related events in NAFLD: A predictive model
Authors: Luis Calzadilla-Bertot, Gary P. Jeffrey, Zhengyi Wang, Yi Huang, George Garas, Michael Wallace, Bastiaan de Boer, Jacob George, Mohammed Eslam, Amy Phu, Javier Ampuero, Ana Lucena Valera, Manuel Romero-Gómez, Rocio Aller de la Fuente, Leon A. Adams
Journal: Hepatology (2023)

Management of NAFLD involves noninvasive prediction of fibrosis, which is a surrogate for patient outcomes. We aimed to develop and validate a model predictive of liver-related events (LREs) of decompensation and/or HCC and compare its accuracy with fibrosis models.
Quantifying days at home in patients with cirrhosis: A national cohort study
Authors: Hirsh Elhence, Jennifer L. Dodge, Albert J. Farias, Brian P. Lee
Journal: Hepatology (2023)

Days at home (DAH) is a patient-centric metric developed by the Medicare Payment Advisory Commission, capturing annual health care use, including and beyond hospitalizations and mortality. We quantified DAH and assessed factors associated with DAH differences among patients with cirrhosis.
Characteristics of individuals with alpha-1 antitrypsin deficiency from Northern and Southern European countries: EARCO international registry
Authors: Marc Miravitlles, Alice M. Turner, María Torres-Duran, Hanan Tanash, Carlota Rodríguez-García, José Luis López-Campos, Jan Chlumsky, Catarina Guimaraes, Juan Luis Rodríguez-Hermosa, Angelo Corsico, Cristina Martinez-González, José María Hernández-Pérez, Ana Bustamante, David G. Parr, Francisco Casas-Maldonado, Ana Hecimovic, Wim Janssens, Beatriz Lara, Miriam Barrecheguren, Cruz González, Jan Stolk, Cristina Esquinas, Christian F. Clarenbach
Journal: European Respiratory Journal (2023)

<b>The EARCO registry contains information on &gt;1000 patients with AATD from 15 countries. The demographic characteristics and the disease characteristics are not significantly different in individuals from Northern or Southern European countries.</b> https://bit.ly/3EdGGcC
If your patient with asthma wheezes when sitting or lying quietly, lung function testing may reveal small airway disease
Authors: Peter B. Noble, Graham M. Donovan
Journal: European Respiratory Journal (2023)

Diagnostic protocols for the assessment of small airway disease have been advanced to optimise the clinical management of patients with asthma <https://bit.ly/3lpECHO> The paradigm of "small airway disease" (SAD) continues to be advanced with considerable enthusiasm by clinicians and scientists alike [1, 2], having full knowledge that the binary classification of airways as "small" or "large" is somewhat arbitrary [3, 4]. Nonetheless, important questions that remain unanswered are: 1) how does SAD manifest; 2) how do we detect SAD, ideally in a cost-effective manner that can be adopted in primary care; and finally 3) once a patient has been classified as having SAD, what can we do about it? The second of these questions is amply addressed in the present issue of the European Respiratory Journal by Kocks et al . [5].
HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer
Authors: Ganji Seeta Rama Raju, Eluri Pavitra, Sai Samyuktha Bandaru, Ganji Lakshmi Varaprasad, Ganji Purnachandra Nagaraju, Rama Rao Malla, Yun Suk Huh, Young-Kyu Han
Journal: Molecular Cancer (2023)

Abstract HOX transcript antisense intergenic RNA (HOTAIR) is an oncogenic non-coding RNA whose expression is strongly correlated with the tumor grade and prognosis of a variety of carcinomas including breast cancer (BC). HOTAIR regulates various target genes via sponging and epigenetic mechanisms and controls various oncogenic cellular and signaling mechanisms including metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by a variety of transcriptional and epigenetic mechanisms. In this review, we describe the regulatory mechanisms that govern HOTAIR expression during cancer development and explore how HOTAIR drives BC development, metastasis, and drug resistance. In the final section of this review, we focus on the role of HOTAIR in BC management, therapeutic treatment, and prognosis, highlighting its potential therapeutic applications.
Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation
Authors: Yukai Lu, Lijing Yang, Mingqiang Shen, Zihao Zhang, Song Wang, Fang Chen, Naicheng Chen, Yang Xu, Hao Zeng, Mo Chen, Shilei Chen, Fengchao Wang, Mengjia Hu, Junping Wang
Journal: Leukemia (2023)

Abstract Hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have robust self-renewal potential, which is responsible for sustaining normal and malignant hematopoiesis, respectively. Although considerable efforts have been made to explore the regulation of HSC and LSC maintenance, the underlying molecular mechanism remains obscure. Here, we observe that the expression of thymocyte-expressed, positive selection-associated 1 (Tespa1) is markedly increased in HSCs after stresses exposure. Of note, deletion of Tespa1 results in short-term expansion but long-term exhaustion of HSCs in mice under stress conditions due to impaired quiescence. Mechanistically, Tespa1 can interact with CSN subunit 6 (CSN6), a subunit of COP9 signalosome, to prevent ubiquitination-mediated degradation of c-Myc protein in HSCs. As a consequence, forcing c-Myc expression improves the functional defect of Tespa1-null HSCs. On the other hand, Tespa1 is identified to be highly enriched in human acute myeloid leukemia (AML) cells and is essential for AML cell growth. Furthermore, using MLL-AF9-induced AML model, we find that Tespa1 deficiency suppresses leukemogenesis and LSC maintenance. In summary, our findings reveal the important role of Tespa1 in promoting HSC and LSC maintenance and therefore provide new insights on the feasibility of hematopoietic regeneration and AML treatment.
Reprogramming anchorage dependency by adherent-to-suspension transition promotes metastatic dissemination
Authors: Hyunbin D. Huh, Yujin Sub, Jongwook Oh, Ye Eun Kim, Ju Young Lee, Hwa-Ryeon Kim, Soyeon Lee, Hannah Lee, Sehyung Pak, Sebastian E. Amos, Danielle Vahala, Jae Hyung Park, Ji Eun Shin, So Yeon Park, Han Sang Kim, Young Hoon Roh, Han-Woong Lee, Kun-Liang Guan, Yu Suk Choi, Joon Jeong, Junjeong Choi, Jae-Seok Roe, Heon Yung Gee, Hyun Woo Park
Journal: Molecular Cancer (2023)

Abstract Background Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge. Methods We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival. Results We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell–matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth. Conclusion We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.
PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy
Authors: Jeremy M. Kelm, Deepti S. Pandey, Evan Malin, Hussein Kansou, Sahil Arora, Raj Kumar, Navnath S. Gavande
Journal: Molecular Cancer (2023)

Molecularly targeted cancer therapies substantially improve patient outcomes, although the durability of their effectiveness can be limited. Resistance to these therapies is often related to adaptive changes in the target oncoprotein which reduce binding affinity. The arsenal of targeted cancer therapies, moreover, lacks coverage of several notorious oncoproteins with challenging features for inhibitor development. Degraders are a relatively new therapeutic modality which deplete the target protein by hijacking the cellular protein destruction machinery. Degraders offer several advantages for cancer therapy including resiliency to acquired mutations in the target protein, enhanced selectivity, lower dosing requirements, and the potential to abrogate oncogenic transcription factors and scaffolding proteins. Herein, we review the development of proteolysis targeting chimeras (PROTACs) for selected cancer therapy targets and their reported biological activities. The medicinal chemistry of PROTAC design has been a challenging area of active research, but the recent advances in the field will usher in an era of rational degrader design.
High night-to-night variability in sleep apnea severity is associated with uncontrolled hypertension
Authors: Bastien Lechat, Kelly A. Loffler, Amy C. Reynolds, Ganesh Naik, Andrew Vakulin, Garry Jennings, Pierre Escourrou, R. Doug McEvoy, Robert J. Adams, Peter G. Catcheside, Danny J. Eckert
Journal: npj Digital Medicine (2023)

Obstructive sleep apnea (OSA) severity can vary markedly from night-to-night. However, the impact of night-to-night variability in OSA severity on key cardiovascular outcomes such as hypertension is unknown. Thus, the primary aim of this study is to determine the effects of night-to-night variability in OSA severity on hypertension likelihood. This study uses in-home monitoring of 15,526 adults with ~180 nights per participant with an under-mattress sleep sensor device, plus ~30 repeat blood pressure measures. OSA severity is defined from the mean estimated apnea-hypopnoea index (AHI) over the ~6-month recording period for each participant. Night-to-night variability in severity is determined from the standard deviation of the estimated AHI across recording nights. Uncontrolled hypertension is defined as mean systolic blood pressure ≥140 mmHg and/or mean diastolic blood pressure ≥90 mmHg. Regression analyses are performed adjusted for age, sex, and body mass index. A total of 12,287 participants (12% female) are included in the analyses. Participants in the highest night-to-night variability quartile within each OSA severity category, have a 50-70% increase in uncontrolled hypertension likelihood versus the lowest variability quartile, independent of OSA severity. This study demonstrates that high night-to-night variability in OSA severity is a predictor of uncontrolled hypertension, independent of OSA severity. These findings have important implications for the identification of which OSA patients are most at risk of cardiovascular harm.
Matrix stiffness regulates osteoclast fate through integrin-dependent mechanotransduction
Authors: Xiaogang Wang, Luli Ji, Jing Wang, Changsheng Liu
Journal: Bioactive Materials (2023)

Osteoclasts ubiquitously participate in bone homeostasis, and their aberration leads to bone diseases, such as osteoporosis. Current clinical strategies by biochemical signaling molecules often perturb innate bone metabolism owing to the uncontrolled management of osteoclasts. Thus, an alternative strategy of precise regulation for osteoclast differentiation is urgently needed. To this end, this study proposed an assumption that mechanic stimulation might be a potential strategy. Here, a hydrogel was created to imitate the physiological bone microenvironment, with stiffnesses ranging from 2.43kPa to 68.2kPa. The impact of matrix stiffness on osteoclast behaviors was thoroughly investigated. Results showed that matrix stiffness could be harnessed for directing osteoclast fate in vitro and in vivo. In particular, increased matrix stiffness inhibited the integrin β3-responsive RhoA-ROCK2-YAP-related mechanotransduction and promoted osteoclastogenesis. Notably, preosteoclast development is facilitated by medium-stiffness hydrogel (M-gel) possessing the same stiffness as vessel ranging from 17.5 kPa to 44.6 kPa by partial suppression of mechanotransduction, which subsequently encouraged revascularization and bone regeneration in mice with bone defects. Our works provide an innovative approach for finely regulating osteoclast differentiation by selecting the optimum matrix stiffness and enable us further to develop a matrix stiffness-based strategy for bone tissue engineering.
Correspondence to “Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers <scp>CD63</scp> and <scp>CD203c</scp> in a prospective study”
Authors: Jessy Elst, Marie‐Line M. van der Poorten, Alessandro Toscano, Athina L. Van Gasse, Christel Mertens, Michiel Beyens, Margo M. Hagendorens, Didier G. Ebo, Vito Sabato
Journal: Allergy (2023)

The authors declare no conflict of interest.
Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities
Authors: Claire Xin Sun, Paul Daniel, Gabrielle Bradshaw, Hui Shi, Melissa Loi, Nicole Chew, Sarah Parackal, Vanessa Tsui, Yuqing Liang, Mateusz Koptyra, Shazia Adjumain, Christie Sun, Wai Chin Chong, Dasun Fernando, Caroline Drinkwater, Motahhareh Tourchi, Dilru Habarakada, Dhanya Sooraj, Diana Carvalho, Phillip B. Storm, Valerie Baubet, Leanne C. Sayles, Elisabet Fernandez, Thy Nguyen, Mia Pörksen, Anh Doan, Duncan E. Crombie, Monty Panday, Nataliya Zhukova, Matthew D. Dun, Louise E. Ludlow, Bryan Day, Brett W. Stringer, Naama Neeman, Jeffrey A. Rubens, Eric H. Raabe, Maria Vinci, Vanessa Tyrrell, Jamie I. Fletcher, Paul G. Ekert, Biljana Dumevska, David S. Ziegler, Maria Tsoli, Nur Farhana Syed Sulaiman, Amos Hong Pheng Loh, Sharon Yin Yee Low, E. Alejandro Sweet-Cordero, Michelle Monje, Adam Resnick, Chris Jones, Peter Downie, Bryan Williams, Joseph Rosenbluh, Daniel Gough, Jason E. Cain, Ron Firestein
Journal: Cancer Cell (2023)
Challenges and opportunities for modeling aging and cancer
Authors: Olga Anczuków, Susie Airhart, Jeffrey H. Chuang, Lisa M. Coussens, George A. Kuchel, Ron Korstanje, Sheng Li, Anna Lisa Lucido, Sandra S. McAllister, Katerina Politi, Kornelia Polyak, Timothy Ratliff, Gary Ren, Jennifer J. Trowbridge, Duygu Ucar, Karolina Palucka
Journal: Cancer Cell (2023)
In This Issue
Journal: Arthritis & Rheumatology (2023)

Daily Prednisone and TCZ Treatment of GCA Affects HbA 1cClinicians have established hemoglobin A 1c (HbA 1c ) as a convenient marker for the diagnosis and monitoring of diabetes.While researchers lack a thorough understanding of the relationship between red blood cell (RBC) count and inflammation, some tory factors may lead to an increased number of young RBCs, which may, in turn, reduce HbA 1c in a glucose-independent manner.Consistent with this hypothesis is the fact that previous studies have documented a quick rise in HbA 1c levels when initiating glucocorticoids (GCs).In this issue, Patel et al (p.586) report that tocilizumab (TCZ) treatment of giant cell arteritis was associated with a substantial reduction in HbA 1c level.The investigators sought to understand the impact of a GC taper and TCZ treatment on HbA 1c levels and analyzed the systematic data collected during the clinical trial of TCZ in GCA known as GiACTA.The detailed longitudinal data spanned 52 weeks and revealed that HbA 1c decreased as the GC daily dose